Molecular mechanisms of pyrethroid insecticide-induced acute kidney injury: a network toxicology and molecular...

Pyrethroid insecticides are widely used globally, but their potential nephrotoxicity has gained increasing attention. Although previous studies suggest pyrethroids may induce acute kidney injury (AKI), the underlying mechanisms remain unclear. This study employed a network toxicology approach to elucidate the molecular mechanisms of pyrethroid-induced AKI. Eight commonly used pyrethroids were analyzed individually. A total of 3203 AKI-related genes were retrieved from public databases, and intersection analysis identified 157-196 common targets for each pyrethroid. Protein-protein interaction (PPI) network integration further identified 18 shared hub targets across the eight pyrethroids, among which 15 were further supported by GEO validation in AKI samples. Notably, 7 targets - SRC, CASP3, ESR1, CCND1, MMP9, BCL2, and HSP90AA1-were consistently shared across all compounds and were therefore considered as core targets. Enrichment analyses indicated that these targets were mainly involved in oxidative stress-, inflammation- and apoptosis-related processes. GEO validation further suggested that these alterations were particularly prominent in renal tubular cells and endothelial cells. Molecular docking supported potential interactions between pyrethroids and the core targets. The findings suggested that pyrethroid-induced AKI may involve processes related to oxidative stress, inflammation, and apoptosis, accompanied by impaired repair responses, ultimately disrupting the balance between injury and regeneration in renal tubular epithelial cells.